The wonder of clotting
Blood clotting is one of the most beautiful and carefully choreographed biological processes that mammalian bodies are capable of. This system is essential for our survival, and is breathtakingly complex. It comprises dozens, possibly hundreds, of elements that must align just-so, in order to prevent that tiny little papercut you barely noticed from causing you to haemorrhage so badly you would die without medical intervention. Equally, over-exuberance of this system would lead to massive clotting and probable death.
I have always been a fan of the coagulation cascade, which is the major effector arm of the blood clotting system. I received my first introduction to it in school, when I was studying human biology. I was mesmerised by its intricacy and synchronization - if one little component doesn't pull its weight, then the whole thing falls apart, as each stage is entirely dependent on preceding ones. It really is a remarkable feat of engineering.
Not everyone shares my appreciation of blood clotting; in fact, I would go so far as to say that whenever I've ventured to broach the subject, I've been told that it's 'weird'. This is most unfair. I have to say, I am so happy that I finally (FINALLY!) get to witter on uninterrupted about how amazing blood clotting is - I love the internet!
I'm not going to give a comprehensive explanation of how it all works here, as many others have done this elsewhere (and their efforts are far superior to any attempt that I could make), and I think this would be somewhat tedious in the present context. Instead, I am going to show a simplified version of events, just to give you an appreciation of how finely-tuned and delicate it all is.
So (deep breath), here goes...
I have always been a fan of the coagulation cascade, which is the major effector arm of the blood clotting system. I received my first introduction to it in school, when I was studying human biology. I was mesmerised by its intricacy and synchronization - if one little component doesn't pull its weight, then the whole thing falls apart, as each stage is entirely dependent on preceding ones. It really is a remarkable feat of engineering.
Not everyone shares my appreciation of blood clotting; in fact, I would go so far as to say that whenever I've ventured to broach the subject, I've been told that it's 'weird'. This is most unfair. I have to say, I am so happy that I finally (FINALLY!) get to witter on uninterrupted about how amazing blood clotting is - I love the internet!
I'm not going to give a comprehensive explanation of how it all works here, as many others have done this elsewhere (and their efforts are far superior to any attempt that I could make), and I think this would be somewhat tedious in the present context. Instead, I am going to show a simplified version of events, just to give you an appreciation of how finely-tuned and delicate it all is.
So (deep breath), here goes...
The coagulation cascade:
The coagulation cascade is the secondary defensive response to blood vessel damage, the primary being the immediate movement of platelets to the site of injury and their aggregation to form a temporary plug. At the same time, the secondary response is underway, which results in the production of fibrin strands that strengthen the platelet plug. The end product is what we know as a clot.
The cascade is mediated by 'factors', known as factor 1 (I), factor 2 (II), factor 5 (V), factor 10 (X), and so on, which are designated by Roman numerals. These factors also have other names but generally they are simply referred to by their numbers. There are two pathways - the intrinsic pathway, which is triggered by the damaged wall of the blood vessel coming into contact with certain circulating elements in the blood, and the extrinsic pathway, which is activated by a chemical called tissue factor that is found on specific cells in the blood. In terms of effecting the cascade, the latter is the more important of the two. As can be seen in the schematic below, they eventually converge on the activation of Factor 10 (FX), to form the common pathway.
Triggering these pathways causes a cascade of reactions, where each reaction is dependent on the one previously occurring, and also acts to initiate the next. Within each of these, one of the previously-mentioned factors becomes active, allowing it to itself activate the next factor in the cascade, and so on, eventually leading to the formation of the most important component of the coagulation cascade: thrombin. Thrombin acts to form fibrin from fibrinogen, which eventually forms the clot, thereby preventing further blood loss.
Importantly, thrombin also activates several factors within the cascade, including Factor 12 (FXII), Factor 8 (FVIII), Factor 5 (FV), and Factor 13 (FXIII).
The cascade is mediated by 'factors', known as factor 1 (I), factor 2 (II), factor 5 (V), factor 10 (X), and so on, which are designated by Roman numerals. These factors also have other names but generally they are simply referred to by their numbers. There are two pathways - the intrinsic pathway, which is triggered by the damaged wall of the blood vessel coming into contact with certain circulating elements in the blood, and the extrinsic pathway, which is activated by a chemical called tissue factor that is found on specific cells in the blood. In terms of effecting the cascade, the latter is the more important of the two. As can be seen in the schematic below, they eventually converge on the activation of Factor 10 (FX), to form the common pathway.
Triggering these pathways causes a cascade of reactions, where each reaction is dependent on the one previously occurring, and also acts to initiate the next. Within each of these, one of the previously-mentioned factors becomes active, allowing it to itself activate the next factor in the cascade, and so on, eventually leading to the formation of the most important component of the coagulation cascade: thrombin. Thrombin acts to form fibrin from fibrinogen, which eventually forms the clot, thereby preventing further blood loss.
Importantly, thrombin also activates several factors within the cascade, including Factor 12 (FXII), Factor 8 (FVIII), Factor 5 (FV), and Factor 13 (FXIII).
How does it end?
Although clotting is good, because it prevents excessive blood loss, unchecked coagulation would be very dangerous. Luckily, there is a counter-balancing anticoagulation mechanism that prevents this. Again, thrombin plays a major role in this (see below). It brings about the activation of Protein C and thrombomodulin, which leads to the inactivation of Factor 5 (FV) and factor 8 (FVIII). In turn, another component called antithrombin prevents thrombin from acting, and interferes with the activation of Factor 10 (FX).
These mechanisms are not static, and there is an ongoing balancing act taking place between the coagulation and anticoagulation systems, in order to optimize blood flow and consistency. The importance of each factor and co-factor (other chemicals that play a role in the process, such as calcium and Vitamin K) is illustrated by the vast array of disorders that can occur if even one element is not functioning properly. The most well-known is the genetic disease Haemophilia A, which results from a lack of Factor 8 (FVIII), where there is excessive bleeding.
The coagulation cascade is a pharmacological target for many therapeutics, including warfarin, which is used as a 'blood thinner' or anticoagulant to prevent the formation of dangerous clots. This is a Vitamin K antagonist, preventing its actions within the cascade, and is also the active ingredient in some rat or mouse poisons (it acts by promoting massive internal haemorrhaging, which is pretty nasty).
In summary...
So, this is my edited and simplified version of the coagulation cascade, and my take on how wonderful it all is... of course it has its limitations, and it's not a perfect system, but I think it's incredibly clever and admire it very much. I hope I've managed to convince you of its loveliness, and now, whenever you get a cut that manages to stop bleeding all by itself, you'll have an appreciation of the amazing work going on behind the scenes in your very own body!